Therapeutic Advances in Chronic Disease最新文献

Background: Pericardial effusion (PE) is an abnormal fluid volume in the pericardial space and is a common clinical entity. The incidence of PE is estimated diversely and depends on risk factors, etiologies, and geographic locations.

Objectives: This study aimed to assess the clinical characteristics, etiologic spectrum, echocardiographic features, and outcomes among patients with different types of PE.

Method: This retrospective observational study included 93 patients with confirmed PE. Their medical records were reviewed in the hospital information system of Mogadishu Somali Turkish Training and Research Hospital between April 2022 and September 2022. Patient demographics, clinical characteristics, chest X-rays, echocardiography, laboratory findings, management approaches, and outcome reports were reviewed and recorded.

Results: Out of the 3000 participants, 3.1% (n = 93/3000) met the definition of definitive PE. In this study, we included 51 females and 42 males. Among the patients, 86% (n = 80) had at least one comorbidity, with diabetes (38.7%) and hypertension (37.6%) being the most common. The most frequently reported clinical presentation findings were shortness of breath (67.7%), chest pain (49.4%), cough (47.3%), and palpitations (47.3%). Cardiac tamponade developed in 9.7% (n = 9) of the patients. Pericardial taps were performed in 64.5% of the cases. Our analysis showed that the most common cause of PE was cardiac disease (n = 33, 35.4%), followed by tuberculosis (TB) (n = 25, 26.8%), uremic pericarditis (n = 24, 25.8%), and hypothyroidism (n = 10, 10.7%). Regarding the severity of PE based on echocardiographic findings, nearly half of the patients (n = 46, 49.4%) had mild PE, whereas 26.8% (n = 25) had moderate PE, and 23.6% (n = 22) had severe PE. Two-thirds of the cases (66.6%) were managed with furosemide, 48 (51.6%) patients were treated with an anti-inflammatory, hemodialysis was performed in 24 (25.8%) patients and antituberculous medications were administered to 7 (7.5%) patients. Out of the 93 patients, 24 (25.8%) died during the hospital stay. It was determined that the mortality risk of patients with renal failure was 7.518 times higher than those without (p = 0.004), and the risk for those with TB was 5.554 times higher than those without (p = 0.011). Other variables were not influential on mortality (p > 0.050).

Conclusion: Our study results demonstrate the epidemiological profile of PE in Somalia. The leading causes of PE were cardiac diseases, uremic pericarditis, TB, and hypothyroidism. PE is a significant cause of morbidity and mortality in Somalia, especially in individuals with renal failure and TB infection.

The development of a biosimilar is based on comparative structural, physicochemical, functional and clinical assessments. The sum of these analyses encompasses the 'totality of evidence', which demonstrates no clinically meaningful differences between the biosimilar and the reference product (RP). Once biosimilarity has been established, provided there is suitable scientific justification, clinical data may be extrapolated to other indications of the RP. AVT02 has been developed as a biosimilar to high-concentration, low-volume Humira (adalimumab), an anti-tumour necrosis factor-alpha monoclonal antibody approved for various chronic inflammatory indications. The totality of evidence for AVT02 is described, supporting its approval as an adalimumab biosimilar for all approved indications globally. Analytical similarity assessments using mass spectrometry methods demonstrated identical amino acid sequences for AVT02 and the RP, with high similarity in terms of primary structure, post-translational modifications and higher-order structural attributes. The mechanism of action was assessed by various cell-based potency assays and binding assays, and the results demonstrated that AVT02 is highly similar to the RP. No clinically meaningful differences in terms of purity, potency and safety were observed, and minor differences in a few physiochemical attributes did not impact the in vitro biologic activity and were not considered clinically relevant. Clinical similarity was demonstrated by comparing the pharmacokinetic, efficacy, safety and immunogenicity profiles of AVT02 with those of the RP. Clinical studies supported similar pharmacokinetic and comparable immunogenicity profiles between AVT02 and the RP in healthy participants and participants with moderate-to-severe chronic plaque psoriasis, with no new safety signals detected. The totality of evidence described demonstrates the biosimilarity of AVT02 to the RP, thereby fulfilling the scientific and regulatory requirements for AVT02 as a high-concentration biosimilar for the treatment of chronic plaque psoriasis and all approved indications of the RP.

Background: The relationship between short-term cardiac function changes and long-term outcomes in heart failure (HF) patients undergoing cardiac resynchronization therapy (CRT) remains uncertain, especially when stratified by diabetes status.

Objectives: This study aims to assess the association between short-term cardiac function changes and outcomes such as all-cause mortality and HF hospitalization in patients undergoing CRT, stratified by diabetes status.

Design: This is a cohort longitudinal retrospective study.

Methods: A total of 666 HF patients, treated with CRT between March 2007 and March 2019, were included in this study. Among them, 166 patients (24.9%) were diagnosed with diabetes. Cardiac function was assessed at baseline and again at 6 months, incorporating evaluations of left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), left atrial diameter (LAD), N-terminal prohormone of brain natriuretic peptide (NT-proBNP), and QRS duration. The QRS duration represents the time required for a stimulus to spread through the ventricles (ventricular depolarization). The primary endpoints of the study were all-cause mortality and HF-related hospitalization.

Results: During a median follow-up of 2.51 years, 172 (25.8%) patients died and 197 (29.6%) were hospitalized for HF. Changes in LVEF, LVEDD, and LAD within 6 months had similar effects on adverse outcomes in both diabetic and nondiabetic patients. However, the presence of diabetes significantly modified the association between changes in NT-proBNP and QRS duration and adverse outcomes. Short-term changes in NT-proBNP and QRS duration were positively associated with all-cause mortality and HF hospitalization in patients without diabetes. However, the relationship between short-term changes in NT-proBNP and QRS duration and adverse outcomes was non-linear in diabetic patients.

Conclusion: Improvement of cardiac function after CRT implantation can reduce long-term risk of all-cause mortality and HF hospitalization in HF patients. However, the presence of diabetes may affect the association between short-term changes in NT-proBNP and QRS duration and adverse outcomes.

Background: The factors affecting cardiovascular risk associated with vascular calcification in patients with chronic kidney disease are less well addressed. Distinct risk factors may contribute synergistically to this elevated cardiovascular risk in this population.

Objectives: We aimed to determine whether echocardiographic left ventricular hypertrophy (LVH) affects the risk of major adverse cardiac events (MACE) associated with vascular calcification in end-stage kidney disease (ESKD) patients.

Methods: In this retrospective cohort study, ESKD patients underwent chest radiography and echocardiography to assess aortic arch calcification (AoAC) and LVH, respectively, and were classified into three groups accordingly: non-to-mild AoAC without LVH, non-to-mild AoAC with LVH, and moderate-to-severe AoAC. The risks of MACE, cardiovascular mortality, and overall mortality were assessed using Cox proportional hazard analysis.

Results: Of the 283 enrolled ESKD patients, 44 (15.5%) had non-to-mild AoAC without LVH, 117 (41.3%) had non-to-mild AoAC with LVH, and 122 (43.1%) had moderate-to-severe AoAC. After 34.1 months, 107 (37.8%) participants developed MACE, including 6 (13.6%), 40 (34.2%), and 61 (50%) from each respective group. Those with moderate-to-severe AoAC (Hazard ratio, 3.72; 95% confidence interval, 1.58-8.73) had a significantly higher risk of MACE than did those with non-to-mild AoAC without LVH or with non-to-mild AoAC and LVH (Hazard ratio, 2.73; 95% confidence interval, 1.16-6.46). A similar trend was observed for cardiovascular and overall mortality.

Conclusion: Echocardiographic LVH could modify the risk of adverse cardiovascular events associated with vascular calcification in ESKD patients. Interventions aiming to ameliorate both morbidities might be translated into a lower MACE risk in this population.

Background: Recent studies suggest that lipid-lowering agents (LLA) may reduce chronic periodontitis, but it is unknown whether this benefit extends to people with type 2 diabetes (T2D).

Objective: We assessed the association between LLA use and periodontitis in Hispanic adults with T2D.

Design: This was a cross-sectional observational study.

Methods: We assessed the association of LLA use and periodontal parameters in 253 Puerto Ricans 40-65 years with T2D who participated in the Lipid-Lowering agents use in Periodontitis and Diabetes Study study. Participants were classified as (a) none- or <1 year, (b) 1-4 years, or (c) >4 years. The primary outcome consists of a tertile percent of sites with probing pocket depth (PPD) ⩾ 4 mm and the secondary outcome includes tertiles of percent sites with clinical attachment loss (CAL) ⩾ 4 mm. Multinomial logistic regression models adjusted for age, gender, smoking status, education, waist circumference, glycosylated hemoglobin A1C (HbA1c), bleeding on probing, examiner, and anti-inflammatory agents were used to estimate the association.

Results: LLA (92.5%, statins) was used by 52% of participants. LLA use 1-4 years was associated with lower odds of PPD ⩾ 4 mm (OR: 0.22, p = 0.005; high versus low tertile) or lower odds of CAL ⩾ 4 mm (OR: 0.33, p = 0.02, middle versus low tertile), compared to those with LLA minimal or no use. This association was lost for participants who used LLA for >4 years. LLA users for >4 years with periodontal disease had elevated HbA1c (OR: 1.36, p = 0.05).

Conclusion: The use of LLA for 1-4 years was associated with lower values of periodontal parameters versus minimal LLA use. This association was not present among people using LLA > 4 years users, but these participants had poorer glycemic control compared to other participants. In this cross-sectional study, the finding that LLA use 1- 4 years is associated with lower values of periodontal parameters of severity in T2D individuals may help clarify some of the controversies regarding the benefit of these medications in this population.

Background: Magnesium (Mg) deficiency is closely linked with proteinuria.

Objectives: To assess the impact of oral Mg citrate supplementation on the clinical outcome of diabetic nephropathy (DN) patients.

Design: This was a prospective, randomized, controlled, open-label study.

Methods: Sixty DN patients were recruited from Nephrology and Endocrinology departments, Ain Shams University Hospitals, Cairo, Egypt. Patients were assigned by stratified randomization based on their Mg status, to either Mg citrate group, (n = 30), who received the standard regimen + oral Mg citrate 2.25 g/day or Control group, (n = 30), who received the standard regimen only. The primary endpoint was a change in urinary albumin to creatinine ratio (UACR) after 12 weeks. Secondary outcomes were insulin resistance, glycemic control, lipid profile, serum osteocalcin, quality of life (QoL) and Mg tolerability.

Results: Out of a total of 60 patients enrolled, only 54 patients (26 in Mg citrate group and 28 in the control group) completed the study. Groups were comparable at baseline. The UACR median percent reduction was significantly higher in the Mg citrate group (-6.87%) versus (-0.9%) in the Control group, p = 0.001. After 12 weeks, the estimated glomerular filtration rate significantly improved in the Mg citrate group versus Control group (p = 0.001). Comparable change was observed in glycemic indices. Lipid profile significantly improved in the Mg citrate group versus Control group (p = 0.001). Serum osteocalcin levels significantly declined in the Mg citrate group (p = 0.001) versus control group. Regarding QoL, the total score and all domains significantly improved in the Mg citrate group compared to control. The Mg supplement was tolerable with only mild reported side effects that required no intervention.

Conclusion: Oral Mg citrate supplementation improved microalbuminuria in DN patients. It also had favorable effects on serum osteocalcin, lipid profile and QoL with no reported major side effects.

Trial registration: ClinicalTrials.gov identifier: NCT03824379.

Background: Patients with symptomatic lower-extremity peripheral artery disease (LE-PAD) are prone to serious cardiovascular and limb events. Few studies have evaluated the effect of rivaroxaban-based dual antithrombotic therapy in high-risk patients with LE-PAD in Asian populations.

Objectives: To investigate the efficacy and safety of rivaroxaban-based dual antithrombotic therapy in symptomatic patients with LE-PAD.

Design: Retrospective cohort study.

Methods: This study included patients with LE-PAD treated at the Nanjing Drum Tower Hospital from 1 January 2018 to 31 December 2021. These participants were divided into antiplatelet (APT) or antiplatelet therapy combined with rivaroxaban (RAPT) groups. The efficacy outcomes in this study were the occurrence of major adverse cardiovascular events (MACE), including myocardial infarction, ischemic stroke, or death from cardiovascular causes, and major adverse limb events (MALE), including urgent revascularization, acute limb ischemia, and major amputation. The safety outcomes included major and clinically relevant non-major (CRNM) bleeding. Patients were followed up until the time of death or the end of the study (31 March 2023).

Results: We included 1144 patients with LE-PAD (APT: 502 patients; RAPT: 642 patients). The RAPT group had a lower risk of primary composite efficacy outcomes [hazard ratio (HR): 0.40] and a nonsignificant increase in major bleeding risk (HR: 2.33) than the APT group. The RATP group also had a significantly lower risk of secondary efficacy outcomes, including ischemic stroke (HR: 0.41), myocardial infarction (HR: 0.31), cardiovascular death (HR: 0.40), and MALE (HR: 0.65), than the APT group. The CRNM bleeding incidence varied between the two groups (HR: 3.96). Moreover, no significant interactions were observed between the subgroups and treatment groups in the composite efficacy analysis.

Conclusion: Rivaroxaban-based dual antithrombotic therapy significantly reduced the occurrence of MACE in patients with LE-PAD without increasing major bleeding events. High-risk patients benefited from the dual antithrombotic therapy.

Background: Diabetic kidney disease (DKD) is a serious diabetic complication and the performance of serum Klotho in DKD's prognostic evaluation is controversial.

Objective: To assess the association of serum Klotho with adverse kidney and non-kidney clinical outcomes in patients with DKD.

Design: Clinical studies regarding the relationship of serum Klotho with DKD were included. Study quality was assessed using the Newcastle-Ottawa scale. Subgroup and sensitive analyses were performed to search for the source of heterogeneity.

Data sources and methods: We comprehensively searched PubMed, Embase, Web of Science, and Cochrane library databases up to 27 September 2022. The associations of Klotho with albuminuria, such as the urinary albumin creatinine ratio (UACR), kidney outcomes such as persistent albuminuria, estimated glomerular filtration rate decline, and non-kidney outcomes such as diabetic retinopathy, cardiovascular morbidity, and mortality, were evaluated. The indicators, such as the correlation coefficient (r), odds ratio (OR), relative risk, and hazard ratio, were retrieved or calculated from the eligible studies.

Results: In all, 17 studies involving 5682 participants fulfilled the inclusion criteria and were included in this meta-analysis. There was no significant association of serum Klotho with UACR in DKD patients [summary r, -0.28 (-0.55, 0.04)] with high heterogeneity. By contrast, a strong association was observed regarding serum Klotho with kidney outcomes [pooled OR, 1.60 (1.15, 2.23)], non-kidney outcomes [pooled OR, 2.78 (2.11, 3.66)], or combined kidney and non-kidney outcomes [pooled OR, 1.96 (1.45, 2.65)] with moderate heterogeneity. Subgroup analysis indicated that age, study design, and the estimated glomerular filtration rate may be the sources of heterogeneity.

Conclusion: A decreased serum Klotho level is possibly associated with an increased risk of developing kidney and non-kidney clinical outcomes in DKD patients; thus, Klotho may be a possible biomarker to predict DKD clinical outcomes. Additional studies are needed to clarify and validate Klotho's prognostic value.